AAT + Corticosteroids for Graft-versus-Host Disease

No longer recruiting at 26 trial locations
TR
Overseen ByTrial Registration Coordinator
Age: Any Age
Sex: Any
Trial Phase: Phase 3
Sponsor: CSL Behring
Must be taking: Corticosteroids
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding alpha-1 antitrypsin (AAT) to corticosteroids is more effective than corticosteroids alone in treating high-risk acute graft-versus-host disease (GVHD). GVHD can occur after a stem cell or bone marrow transplant when donor cells attack the recipient's body. The study will compare the effects of AAT with a placebo (a substance with no active drug) to determine if AAT improves treatment outcomes. Individuals who have recently developed acute GVHD after a transplant and require steroid treatment might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not take other drugs for the treatment of GVHD and that you haven't received systemic corticosteroids for any reason within 7 days before the onset of acute GVHD.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that alpha-1 antitrypsin (AAT) is generally safe for people. In past studies, researchers used AAT to treat conditions like acute graft-versus-host disease (GVHD). Participants who received AAT reported only minor side effects, indicating that the treatment is well-tolerated. Earlier studies also found that AAT might help patients by providing long-lasting benefits without causing harm. Although AAT is not a new drug, its use in treating GVHD appears promising with a good safety record.12345

Why do researchers think this study treatment might be promising?

Most treatments for graft-versus-host disease (GVHD) rely on corticosteroids to suppress the immune system. However, the investigational treatment, alpha-1 antitrypsin (AAT), offers a unique approach by targeting inflammation at its source. AAT is a protein that naturally helps control inflammation, and researchers are excited about its potential to reduce the harmful immune response associated with GVHD. Unlike standard treatments, which broadly suppress the immune system, AAT specifically aims to protect tissues from inflammatory damage, potentially offering a more targeted and less immunosuppressive option.

What evidence suggests that AAT with corticosteroids could be an effective treatment for acute GVHD?

In this trial, participants will receive either alpha-1 antitrypsin (AAT) or a placebo. Earlier research has shown that AAT holds promise in treating acute graft-versus-host disease (GVHD). Specifically, AAT infusions produced lasting positive effects for patients whose GVHD did not improve with steroids. These studies also found that AAT had few side effects and low infection rates. The treatment reduces inflammation, which is crucial in managing GVHD. Overall, early findings suggest AAT could be a strong option for those dealing with this condition.23467

Who Is on the Research Team?

SD

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

This trial is for patients aged 12 or older who have acute GVHD after a stem cell transplant and need systemic therapy with corticosteroids. It's not for those previously treated with AAT, having cancer that's returned or not responding to treatment, using steroids within the last week before GVHD onset, or currently on other drugs for GVHD.

Inclusion Criteria

I am 12 years old or older.
I have had a transplant from any donor or undergone any intensity of preparation treatment.
I have acute GVHD after a stem cell transplant.
See 1 more

Exclusion Criteria

My cancer has come back or is getting worse.
I have chronic GVHD or overlap syndrome that started before or at the time of joining.
I started taking systemic corticosteroids within 7 days before my acute GVHD symptoms began.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AAT with corticosteroids or corticosteroids alone for the treatment of high-risk acute GVHD

28 days
Weekly visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for overall survival, progression-free survival, and chronic GVHD

up to 12 months post-randomization

What Are the Treatments Tested in This Trial?

Interventions

  • Alpha-1 antitrypsin (AAT)
  • Placebo
Trial Overview The study compares two treatments for acute GVHD: one group receives Alpha-1 antitrypsin (AAT) plus corticosteroids, while the other gets a placebo alongside corticosteroids. The goal is to see if adding AAT improves outcomes.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: AATExperimental Treatment1 Intervention
Group II: PlaceboPlacebo Group1 Intervention

Alpha-1 antitrypsin (AAT) is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Alpha-1 antitrypsin for:
🇪🇺
Approved in European Union as Alpha-1 antitrypsin for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials
204
Recruited
1,207,000+
Dr. Paul McKenzie profile image

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte profile image

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

National Institutes of Health (NIH)

Collaborator

Trials
2,896
Recruited
8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Blood and Marrow Transplant Clinical Trials Network

Collaborator

Trials
51
Recruited
14,600+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials
3,987
Recruited
47,860,000+

Citations

Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute ...This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after ...
α1-Antitrypsin infusion for treatment of steroid-resistant acute ...AAT infusion produced a high proportion of durable clinical responses in SR-aGVHD. AAT is associated with minimal toxicity and low rates of infection in ...
Alpha-1-Proteinase Inhibitors: Aralast NP - Prolastin®-CAcute Graft Versus Host Disease (aGVHD): Coverage will be provided for a maximum of 8 doses. (4 weeks) and may NOT be renewed. II. Dosing Limits.
Alpha1-Proteinase Inhibitors - Medical Clinical Policy ...The assessment found that, in controlled trials, augmentation therapy has not shown reduced lung function impairment in patients with AAT deficiency and chronic ...
Stage 1 Study of ARALAST NP and GLASSIA in A1PI ...The purpose of this study is to conduct a pilot study to evaluate the safety and efficacy of weekly administration of Alpha1- Proteinase Inhibitor ( A1PI ) ...
Study Details | NCT01523821 | Alpha 1 Anti-Trypsin (AAT) ...This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD)
α1-Antitrypsin infusion for treatment of steroid-resistant acute ...Key Points. AAT infusion produced a high proportion of durable clinical responses in SR-aGVHD.AAT is associated with minimal toxicity and ...
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